Research Highlight

How a faulty protein wreaks havoc in the brain

doi:10.1038/nindia.2016.114 Published online 31 August 2016

Researchers have gained new insights into how the twisted coil of a protein called tau form amyloid fibrils, which cause Alzheimer’s disease and other neurological disorders1. These insights may yield ways for preventing fibril formation, thereby opening therapeutic avenues for various brain disorders including Alzheimer’s disease.

In healthy nerve cells, tau protein helps stabilize microtubules, which act as highways for transporting cellular cargo inside cells. When tau protein forms fibrils, such transportation collapses, destroying nerve cells and leading to brain disorders.

To better understand how tau protein forms fibrils, the researchers synthesized peptides that are specific amino acid sequences of tau protein that form the core of the fibril. They studied the aggregation kinetics and fibril-forming potential of the peptides in solutions by using nuclear magnetic resonance spectroscopy and a fluorescent dye.

All the peptides formed fibrils, but their structure and aggregation kinetics differed. The scientists measured the time for peptide aggregation and found that the fibril-forming potential increases with longer rates of aggregation.

Of the peptides, the researchers focused on R3-S316P, which has two forms — cis-P316 and trans-P316. The cis-P316 form aggregates, whereas the trans-P316 form does not. This suggests that stabilizing the trans-form could prevent tau aggregation.

“It is a logical step to stop the generation of slow-aggregating peptides, which eventually cause brain disorders such as Alzheimer’s disease,” says lead researcher Vinesh Vijayan from the Indian Institute of Science Education and Research, Trivandrum.


1. Jiji, A. C. et al. Direct observation of aggregation-induced backbone conformational changes in tau peptides. Angew. Chem. Int. Ed. (2016) doi: 10.1002/anie.201606544